This Program Project Grant Application for Oncogenic Viruses is concerned with six major areas of research on oncornaviruses. (1) Studies will be carried out on the detailed ultrastructural features of C-type and B-type viruses and their morphological precursors. (2) Immunogenetic and cytogenetic studies will be directed toward defining the relationship of proviral mouse leukemia virus genomes and host genetic loci involved in leukemogenesis, especially as regards the number of different proviruses in mouse cells and their chromosomal locations. The viral genome will also be characterized by analysis of conditional-lethal mutants. (3) Physical and chemical properties of viral nucleic acids will be determined in relation to the mechanism of virus-directed DNA synthesis and the nature of the reverse transcriptase products, both in vitro and in vivo. (4) Virus specific proteins, both virion-associated and non-virion-associated, will be characterized by biochemical and serological techniques. (5) The phenomena of defective virion production or the absence of virion production in certain virally transformed cells will be analyzed in several sarcoma and leukemia virus systems. (6) Factors governing susceptibility to viral oncogenesis in animals will be studied in terms of immune response mechanisms, epidemiology and vaccine development, and synergistic effects between different viruses.